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1.
Ophthalmic Physiol Opt ; 43(5): 947-953, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37184092

RESUMO

PURPOSE: Recent evidence suggests that the ciliary muscle apical fibres are most responsive to accommodative load; however, the structure of the ciliary muscle in individuals with accommodative insufficiency is unknown. This study examined ciliary muscle structure in individuals with accommodative insufficiency (AI). We also determined the response of the ciliary muscle to accommodative/vergence therapy and increasing accommodative demands to investigate the muscle's responsiveness to workload. METHODS: Subjects with AI were enrolled and matched by age and refractive error with subjects enrolled in another ciliary muscle study as controls. Anterior segment optical coherence tomography was used to measure the ciliary muscle thickness (CMT) at rest (0D), maximum thickness (CMTMAX) and over the area from 0.75 mm (CMT0.75) to 3 mm (CMT3) posterior to the scleral spur of the right eye. For those with AI, the ciliary muscle was also measured at increasing levels of accommodative demand (2D, 4D and 6D), both before and after accommodative/vergence therapy. RESULTS: Sixteen subjects with AI (mean age = 17.4 years, SD = 8.0) were matched with 48 controls (mean age = 17.8 years, SD = 8.2). On average, the controls had 52-72 µm thicker ciliary muscles in the apical region at 0D than those with AI (p = 0.03 for both CMTMAX and CMT 0.75). Differences in thickness between the groups in other regions of the muscle were not statistically significant. After 8 weeks of accommodative/vergence therapy, the CMT increased by an average of 22-42 µm (p ≤ 0.04 for all), while AA increased by 7D (p < 0.001). CONCLUSIONS: This study demonstrated significantly thinner apical ciliary muscle thickness in those with AI and that the ciliary muscle can thicken in response to increased workload. This may explain the mechanism for improvement in signs and symptoms with accommodative/vergence therapy.


Assuntos
Presbiopia , Erros de Refração , Humanos , Adolescente , Acomodação Ocular , Corpo Ciliar/diagnóstico por imagem , Corpo Ciliar/fisiologia , Músculo Liso
2.
J Math Biol ; 85(5): 47, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207613

RESUMO

In this paper, we investigate the maximization of the total population of a single species which is governed by a stationary diffusive logistic equation with a fixed amount of resources. For large diffusivity, qualitative properties of the maximizers like symmetry will be addressed. Our results are in line with previous findings which assert that for large diffusion, concentrated resources are favorable for maximizing the total population. Then, an optimality condition for the maximizer is derived based upon rearrangement theory. We develop an efficient numerical algorithm applicable to domains with different geometries in order to compute the maximizer. It is established that the algorithm is convergent. Our numerical simulations give a real insight into the qualitative properties of the maximizer and also lead us to some conjectures about the maximizer.


Assuntos
Algoritmos , Difusão , Modelos Logísticos
3.
Ophthalmic Physiol Opt ; 42(4): 897-903, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35292999

RESUMO

PURPOSE: The relationship between ciliary muscle thickness (CMT), age and refractive error was investigated to determine if CMT, like other anterior ocular anatomy, differs in adults with Down syndrome (DS). METHODS: The CMT of 33 adults with DS was imaged using anterior segment optical coherence tomography. Images from the right eye obtained 45 minutes after cycloplegia (1% tropicamide, 2.5% phenylephrine) were analysed to calculate thickness at 1, 2 and 3 mm posterior to the scleral spur (CMT1, CMT2, CMT3), maximum thickness (CMTMAX) and apical thickness (AT = CMT1 - CMT2). Spherical equivalent refractive error was determined by clinical refraction using both non-dilated and dilated measures. Multivariate regression analysis evaluated the relationship between CMT and refractive error while controlling for subject age. RESULTS: Images were analysed from 26 subjects (mean age (SD) 29 years; mean refractive error (SD): -0.90 (5.03) D, range: -15.75 to +5.13D). Mean (SD) CMT decreased with posterior position (CMT1: 804 (83) µm; CMT2: 543 (131) µm; CMT3: 312 (100) µm). Mean (SD) CMTMAX and AT was 869 (57) µm and 260 (84) µm, respectively. There was a significant linear correlation indicating thinning CMT with increasing age for CMT1 and CMT2 (p ≤0.05). CMT2 and CMT3 had a significant negative correlation (thicker muscle with increasing myopic refractive error) (p ≤0.01). AT had a significant positive correlation (thicker muscle with increasing hyperopic refractive error) (p <0.01). CONCLUSIONS: Ciliary muscle thickness in participants with DS was found to be in a similar range with similar refractive error trends to previous reports of individuals without DS. However, it is important to note that the refractive error trends were driven by individuals with moderate to high levels of myopia.


Assuntos
Síndrome de Down , Miopia , Erros de Refração , Adulto , Corpo Ciliar/diagnóstico por imagem , Síndrome de Down/complicações , Humanos , Músculo Liso , Miopia/diagnóstico , Tomografia de Coerência Óptica/métodos
4.
ACS Infect Dis ; 7(8): 2176-2191, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34218660

RESUMO

Anthrax is caused by Bacillus anthracis and can result in nearly 100% mortality due in part to anthrax toxin. Antimalarial amodiaquine (AQ) acts as a host-oriented inhibitor of anthrax toxin endocytosis. Here, we determined the pharmacokinetics and safety of AQ in mice, rabbits, and humans as well as the efficacy in the fly, mouse, and rabbit models of anthrax infection. In the therapeutic-intervention studies, AQ nearly doubled the survival of mice infected subcutaneously with a B. anthracis dose lethal to 60% of the animals (LD60). In rabbits challenged with 200 LD50 of aerosolized B. anthracis, AQ as a monotherapy delayed death, doubled the survival rate of infected animals that received a suboptimal amount of antibacterial levofloxacin, and reduced bacteremia and toxemia in tissues. Surprisingly, the anthrax efficacy of AQ relies on an additional host macrophage-directed antibacterial mechanism, which was validated in the toxin-independent Drosophila model of Bacillus infection. Lastly, a systematic literature review of the safety and pharmacokinetics of AQ in humans from over 2 000 published articles revealed that AQ is likely safe when taken as prescribed, and its pharmacokinetics predicts anthrax efficacy in humans. Our results support the future examination of AQ as adjunctive therapy for the prophylactic anthrax treatment.


Assuntos
Antraz , Bacillus anthracis , Amodiaquina , Animais , Antraz/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Levofloxacino , Camundongos , Coelhos , Revisões Sistemáticas como Assunto
5.
J Ophthalmol ; 2020: 6613066, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33489336

RESUMO

PURPOSE: This study investigated how a conscious change in ocular accommodation affects intraocular pressure (IOP) and ocular biometrics in healthy adult volunteers of different ages. METHODS: Thirty-five healthy volunteers without ocular disease or past ocular surgery, and with refractive error between -3.50 and +2.50 diopters, were stratified into 20, 40, and 60 year old (y.o.) age groups. Baseline measurements of central cornea thickness, anterior chamber depth, anterior chamber angle, cornea diameter, pupil size, and ciliary muscle thickness were made by autorefraction and optical coherence tomography (OCT), while IOP was measured by pneumotonometry. Each subject's right eye focused on a target 40 cm away. Three different tests were performed in random order: (1) 10 minutes of nonaccommodation (gazing at the target through lenses that allowed clear vision without accommodating), (2) 10 minutes of accommodation (addition of a minus 3 diopter lens), and (3) 10 minutes of alternating between accommodation and nonaccommodation (1-minute intervals). IOP was measured immediately after each test. A 20-minute rest period was provided between tests. Data from 31 subjects were included in the study. ANOVA and paired t-tests were used for statistical analyses. RESULTS: Following alternating accommodation, IOP decreased by 0.7 mmHg in the right eye when all age groups were combined (p = 0.029). Accommodation or nonaccommodation alone did not decrease IOP. Compared to the 20 y.o. group, the 60 y.o. group had a thicker ciliary muscle within 75 µm of the scleral spur, a thinner ciliary muscle at 125-300 µm from the scleral spur, narrower anterior chamber angles, shallower anterior chambers, and smaller pupils during accommodation and nonaccommodation (p's < 0.01). CONCLUSION: Alternating accommodation, but not constant accommodation, significantly decreased IOP. This effect was not lost with aging despite physical changes to the aging eye. A greater accommodative workload and/or longer test period may improve the effect.

6.
Psychiatry Res ; 221(2): 169-71, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24377834

RESUMO

We used magnetic resonance imaging to investigate brain gyrification patterns between 19 children with attention-deficit/hyperactivity disorder (ADHD), 9 children with velocardiofacial syndrome (VCFS), and 23 control children. We found that VCFS is associated with widespread decreases in gyrification. In ADHD, we found minor differences from control children. No evidence was found for common gyrification patterns between VCFS and ADHD children.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Córtex Cerebral/patologia , Síndrome de DiGeorge/patologia , Imageamento por Ressonância Magnética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Estudos de Casos e Controles , Córtex Cerebral/anormalidades , Criança , Síndrome de DiGeorge/complicações , Feminino , Humanos , Masculino , Projetos Piloto , Adulto Jovem
7.
Optom Vis Sci ; 90(11): 1312-20, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24100479

RESUMO

PURPOSE: The purpose of this study was to investigate the relationships between ciliary muscle thickness (CMT), refractive error, and axial length both across subjects and between the more and less myopic eyes of adults with anisometropia. METHODS: Both eyes of 29 adult subjects with at least 1.00 D of anisometropia were measured. Ciliary muscle thickness was measured at the maximum thickness (CMTMAX) and at 1.0 (CMT1), 2.0 (CMT2), and 3.0 mm (CMT3) posterior to the scleral spur, and also at the apical region (Apical CMTMAX = CMTMAX - CMT2, and Apical CMT1 = CMT1 - CMT2). Multilevel regression models were used to determine the relationship between the various CMT measures and cycloplegic refractive error or axial length, and to assess whether there are CMT differences between the more and less myopic eyes of an anisometropic adult. RESULTS: CMTMAX, CMT1, CMT2, and CMT3 were negatively associated with mean refractive error (all p ≤ 0.03), and the strongest association was in the posterior region (CMT2 and CMT3). Apical CMTMAX and Apical CMT1, however, were positively associated with mean refractive error (both p < 0.0001) across subjects. Within a subject, i.e., comparing the two anisometropic eyes, there was no statistically significant difference in CMT in any region. CONCLUSIONS: Similar to previous studies, across anisometropic subjects, a thicker posterior region of the ciliary muscle (CMT2 and CMT3) was associated with increased myopic refractive error. Conversely, shorter, more hyperopic eyes tended to have thicker anterior, apical fiber portions of their ciliary muscle (Apical CMTMAX and Apical CMT1). There was no difference between the two eyes for any CMT measurement, indicating that in anisometropia, an eye can grow longer and more myopic than its fellow eye without resulting in an increase in CMT.


Assuntos
Anisometropia/diagnóstico , Corpo Ciliar/patologia , Músculo Liso/patologia , Miopia/diagnóstico , Acomodação Ocular/fisiologia , Adulto , Comprimento Axial do Olho/patologia , Feminino , Humanos , Masculino , Tomografia de Coerência Óptica , Adulto Jovem
8.
Invest Ophthalmol Vis Sci ; 54(7): 4710-6, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23761093

RESUMO

PURPOSE: To determine if there is a relationship between refractive error and ciliary muscle thickness in different muscle regions. METHODS: An anterior segment optical coherence tomographer was used to measure cycloplegic ciliary muscle thicknesses at 1 mm (CMT1), 2 mm (CMT2), and 3 mm (CMT3) posterior to the scleral spur; maximum (CMTMAX) thickness was also assessed. An autorefractor was used to determine cycloplegic spherical equivalent refractive error (SPHEQ). Apical ciliary muscle fibers were obtained by subtracting corresponding CMT2 values from CMT1 and CMTMAX. Multilevel regression models were used to determine the relationship between ciliary muscle thickness in various regions of the muscle and refractive error. RESULTS: Subjects included 269 children with a mean age of 8.71 ± 1.51 years and a mean refractive error of +0.41 ± 1.29 diopters. In linear models with ciliary muscle thicknesses and SPHEQ, SPHEQ was significantly associated only with CMT2 (ß = -11.34, P = 0.0008) and CMT 3 (ß = -6.97, P = 0.007). When corresponding values of CMT2 were subtracted from CMT1 and CMTMAX, apical fibers at CMT1 (ß = 14.75, P < 0.0001) and CMTMAX (ß = 18.16, P < 0.0001) had a significant relationship with SPHEQ. CONCLUSIONS: These data indicated that in children the posterior ciliary muscle fibers are thicker in myopia (CMT2 and CMT3), but paradoxically, the apical ciliary muscle fibers are thicker in hyperopia (CMTMAX and CMT1). This may be the first evidence that hyperopia is associated with a thicker apical ciliary muscle region.


Assuntos
Corpo Ciliar/patologia , Músculo Liso/patologia , Erros de Refração/patologia , Adolescente , Criança , Feminino , Humanos , Masculino , Modelos Biológicos , Estudos Prospectivos , Análise de Regressão , Tomografia de Coerência Óptica
9.
Invest Ophthalmol Vis Sci ; 54(2): 1095-105, 2013 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-23287789

RESUMO

PURPOSE: To calculate age-related and per diopter (D) accommodative changes in crystalline lens and ciliary muscle dimensions in vivo in a single cohort of emmetropic human adults ages 30 to 50 years. METHODS: The right eyes of 26 emmetropic adults were examined using ultrasonography, phakometry, anterior segment optical coherence tomography, and high resolution magnetic resonance imaging. Accommodation was measured both subjectively and objectively. RESULTS: In agreement with previous research, older age was linearly correlated with a thicker lens, steeper anterior lens curvature, shallower anterior chamber, and lower lens equivalent refractive index (all P < 0.01). Age was not related to ciliary muscle ring diameter (CMRD) or lens equatorial diameter (LED). With accommodation, lens thickness increased (+0.064 mm/D, P < 0.001), LED decreased (-0.075 mm/D, P < 0.001), CMRD decreased (-0.105 mm/D, P < 0.001), and the ciliary muscle thickened anteriorly (+0.013 to +0.026 mm/D, P < 0.001) and thinned posteriorly (-0.011 to -0.015, P < 0.01). The changes per diopter of accommodation in LED, CMRD, and ciliary muscle thickness were not related to subject age. CONCLUSIONS: The per diopter ciliary muscle contraction is age independent, even as total accommodative amplitude declines. Quantifying normal biometric dimensions of the accommodative structures and changes with age and accommodative effort will further the development of new IOLs designed to harness ciliary muscle forces.


Assuntos
Acomodação Ocular/fisiologia , Envelhecimento/fisiologia , Corpo Ciliar/fisiologia , Emetropia/fisiologia , Cristalino/fisiologia , Músculo Liso/fisiologia , Adulto , Biometria , Corpo Ciliar/anatomia & histologia , Feminino , Humanos , Cristalino/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Liso/anatomia & histologia , Refração Ocular/fisiologia , Tomografia de Coerência Óptica , Ultrassonografia , Acuidade Visual/fisiologia
10.
Hum Brain Mapp ; 34(5): 1230-44, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22331577

RESUMO

Human brains are highly convoluted surfaces with multiple folds. To characterize the complexity of these folds and their relationship with neurological and psychiatric conditions, different techniques have been developed to quantify the folding patterns, also known as the surface complexity or gyrification of the brain. In this study, the authors propose a new geometric approach to measure the gyrification of human brains from magnetic resonance images. This approach is based on intrinsic 3D measurements that relate the local brain surface area to the corresponding area of a tightly wrapped sheet. The authors also present an adaptation of this technique in which the geodesic depth is incorporated into the gyrification computation. These gyrification measures are efficiently and accurately computed by solving geometric partial differential equations. The presentation of the geometric framework is complemented with experimental results for brain complexity in typically developing children and adolescents. Using this novel approach, the authors provide evidence for a gradual decrease in brain surface complexity throughout childhood and adolescence. These developmental differences occur earlier in the occipital lobe and move anterior as children progress into young adulthood.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/crescimento & desenvolvimento , Processamento de Imagem Assistida por Computador , Adolescente , Fatores Etários , Análise de Variância , Criança , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
11.
Optom Vis Sci ; 89(10): 1507-11, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22922779

RESUMO

PURPOSE: To objectively measure changes in the human ciliary muscle dimensions in vivo after instillation of topical phenylephrine, a mydriatic and vasodilating agent. METHODS: A cross-sectional study of 25 healthy young adults was conducted. Measurements of pupil size, accommodation, and ciliary muscle thickness were made both before and 30 min after instillation of 1% proparacaine and 2.5% phenylephrine. Accommodation was measured in three ways: subjectively using a push-up technique and Royal Air Force (RAF) rule, and objectively using both the Grand Seiko autorefractor and PowerRefractor. Images of the temporal ciliary muscle were acquired using the Visante Anterior Segment Optical Coherence Tomographer (OCT). Ciliary muscle images were objectively analyzed using a computer-based segmentation technique. RESULTS: Amplitude of accommodation using the push-up test was reduced by about 1 D with phenylephrine (p < 0.001). Phenylephrine did not change the accommodative response to a 4 D Badal target as measured by either autorefraction or photorefraction (p > 0.30). There was statistically significant thickening of the anterior region and thinning of the posterior region of the ciliary muscle with accommodation (p < 0.001, all locations). Phenylephrine did not affect either baseline ciliary muscle thickness or the accommodative contraction of the muscle (p > 0.09). CONCLUSIONS: Low-dose phenylephrine does not affect ciliary muscle dimensions, ciliary muscle contractility, or accommodative response to a 4 D near target.


Assuntos
Acomodação Ocular/efeitos dos fármacos , Corpo Ciliar/efeitos dos fármacos , Fenilefrina/administração & dosagem , Refração Ocular/fisiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Midriáticos/administração & dosagem , Soluções Oftálmicas , Valores de Referência , Refração Ocular/efeitos dos fármacos , Tomografia de Coerência Óptica , Adulto Jovem
12.
Optom Vis Sci ; 89(5): 719-26, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22504328

RESUMO

PURPOSE: To develop a measurement protocol for changes in the shape and size of the ciliary muscle with accommodation using the Zeiss Visante™ anterior segment optical coherence tomography (AS-OCT) and to determine the test-retest repeatability of these measurements. METHODS: Subjects were 25 adults aged 23 to 28 years. The ciliary muscle was imaged at two visits with the Visante™ while accommodative response was monitored during imaging using the PowerRefractor. Ciliary muscle thickness (CMT) was measured at 1 mm (CMT1), 2 mm (CMT2), and 3 mm (CMT3) posterior to the scleral spur and at the point of maximal thickness (CMTMAX). Thickness was measured at these locations while subjects viewed a target at distance and at a 4.00 D accommodative stimulus. Outcome measures were the change in thickness between distance and the 4.00 D stimulus and the change in thickness per diopter of accommodative response (PowerRefractor). Finally, the repeatability measurements between visit 1 and visit 2 were determined with a Bland-Altman analysis. RESULTS: The statistically significant modeled changes in CMT were as follows: CMTMAX = 69.2 µm (4.00 D stimulus) and 18.1 µm (per diopter of accommodation); CMT1 = 45.2 µm (4.00 D stimulus) and 12.3 µm (per diopter of accommodation); and CMT3 = -45.9 µm (4.00 D stimulus) and -12.0 µm (per diopter of accommodation); p < 0.0001 for all. CONCLUSIONS: The combination of the Visante™ and the PowerRefractor is a feasible tool for measuring thickening of ciliary muscle at more anterior locations and thinning at more posterior locations during accommodation. We noted a wide range of accommodative responses during the time of image capture in this study indicating that the most accurate estimates of the change in ciliary muscle dimensions with accommodation may be obtained by using accommodative response rather than stimulus values and by using measurements taken simultaneously with image capture.


Assuntos
Acomodação Ocular/fisiologia , Corpo Ciliar/patologia , Corpo Ciliar/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/diagnóstico , Cristalino/fisiopatologia , Adulto , Capilares/citologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/fisiopatologia , Diagnóstico Diferencial , Progressão da Doença , Angiofluoresceinografia , Seguimentos , Fóvea Central/irrigação sanguínea , Fóvea Central/patologia , Fundo de Olho , Humanos , Masculino , Oftalmoscopia/métodos , Vasos Retinianos/patologia , Fatores de Tempo , Tomografia de Coerência Óptica
13.
Optom Vis Sci ; 89(5): 727-37, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22504329

RESUMO

PURPOSE: To investigate the morphology of the ciliary muscle during the act of accommodation in a population of children. METHODS: Thirty children aged 6 to 12 years were enrolled. Accommodative response was measured through habitual correction. Height was measured as a control variable. Central axial length was measured with the IOLMaster. Four images of the temporal ciliary muscle were taken with the Visante Optical Coherence Tomographer at three different stimulus levels (0, 4, and 6 D) while accommodative response was monitored concurrently with the PowerRefractor. Accommodative response monitoring was time-matched to ciliary muscle image capture, and the mean was calculated for 5 s surrounding this time point. Four cycloplegic images of the temporal ciliary muscle were also taken. Ciliary muscle thickness measurements were made at the point of maximum thickness (CMTMAX) and at 1 mm (CMT1), 2 mm (CMT2) and 3 mm (CMT3) posterior to the sclera spur. RESULTS: Increasing accommodative response was correlated with increases in the thickness of CMTMAX (p = <0.001) and CMT1 (p = <0.001) and decreases in the thickness of CMT3 (p = <0.001). Thicker values of CMTMAX under cycloplegic conditions were significantly correlated with values of CMTMAX (p = <0.001) and CMT1 (p = 0.001) while accommodating and approached significance in modeling CMT3 (p = 0.06). Mean axial length was correlated with the amount of thinning at CMT3 with accommodation (p = 0.002). Axial length was not significantly correlated with thickness values at CMTMAX (p = 0.7) or CMT1 (p = 0.6). CONCLUSIONS: In a manner similar to previous adult studies, ciliary muscle thickness at CMTMAX and CMT1 increased with accommodation and CMT3 thinned with accommodation. Further investigation is necessary to determine whether CMT2 is a "fulcrum" point along the length of the ciliary muscle where the net change with accommodation is always zero or whether that point varies across subjects or with varying levels of accommodative effort.


Assuntos
Acomodação Ocular/fisiologia , Corpo Ciliar/patologia , Corpo Ciliar/fisiopatologia , Cristalino/fisiopatologia , Erros de Refração/patologia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Hipertrofia/patologia , Hipertrofia/fisiopatologia , Masculino , Prognóstico , Erros de Refração/fisiopatologia , Índice de Gravidade de Doença , Tomografia de Coerência Óptica
14.
Ann Biomed Eng ; 40(9): 1903-16, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22527011

RESUMO

The mitochondrial network is dynamic with conformations that vary between a tubular continuum and a fragmented state. The equilibrium between mitochondrial fusion/fission, as well as the organelle motility, determine network morphology and ultimately mitochondrial/cell function. Network morphology has been linked with the energy state in different cell types. In this study, we examined how bioenergetic factors affect mitochondrial dynamics/motility in cultured vascular endothelial cells (ECs). ECs were transduced with mitochondria-targeted green fluorescent protein (mito-GFP) and exposed to inhibitors of oxidative phosphorylation (OXPHOS) or ATP synthesis. Time-lapse fluorescence videos were acquired and a mathematical program that calculates size and speed of each mitochondrial object at each time frame was developed. Our data showed that inner mitochondrial membrane potential (ΔΨ(m)), ATP produced by glycolysis, and, to a lesser degree, ATP produced by mitochondria are critical for maintaining the mitochondrial network, and different metabolic stresses induce distinct morphological patterns (e.g., mitochondrial depolarization is necessary for "donut" formation). Mitochondrial movement, characterized by Brownian diffusion with occasional bursts in displacement magnitude, was inhibited under the same conditions that resulted in increased fission. Hence, imaging/mathematical analysis shed light on the relationship between bioenergetics and mitochondrial network morphology; the latter may determine EC survival under metabolic stress.


Assuntos
Metabolismo Energético , Células Endoteliais da Veia Umbilical Humana/fisiologia , Mitocôndrias/fisiologia , Dinâmica Mitocondrial , Trifosfato de Adenosina/fisiologia , Células Cultivadas , Humanos , Processamento de Imagem Assistida por Computador , Potencial da Membrana Mitocondrial
15.
Wound Repair Regen ; 20(1): 114-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22211391

RESUMO

Cutaneous burn wounds represent a significant public health problem with 500,000 patients per year in the USA seeking medical attention. Immediately after skin burn injury, the volume of the wound burn expands due to a cascade of chemical reactions, including lipid peroxidation chain reactions. Such expansion threatens life and is therefore highly clinically significant. Based on these chemical reactions, the present paper develops for the first time a three-dimensional mathematical model to quantify the propagation of tissue damage within 12 hours post initial burn. We use the model to investigate the effect of supplemental antioxidant vitamin E for intercepting propagation. We show, for example, that if tissue levels of vitamin E tocotrienol are increased, postburn, by five times then this would slow down the lipid peroxide propagation by at least 50%. We chose the alpha-tocotrienol form of vitamin E as it is a potent inhibitor of 12-lipoxygenase, which is known to propagate oxidative lipid damage. Our model is formulated in terms of differential equations, and sensitivity analysis is performed on the parameters to ensure the robustness of the results.


Assuntos
Antioxidantes/farmacologia , Araquidonato 12-Lipoxigenase/efeitos dos fármacos , Queimaduras/metabolismo , Peroxidação de Lipídeos , Modelos Teóricos , Substâncias Protetoras/farmacologia , Tocotrienóis/farmacologia , Queimaduras/enzimologia , Queimaduras/fisiopatologia , Inibidores Enzimáticos/farmacologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fatores de Tempo , Estados Unidos
16.
Optom Vis Sci ; 88(2): 275-89, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21169877

RESUMO

PURPOSE: To develop and evaluate a semiautomatic algorithm for segmentation and morphological assessment of the dimensions of the ciliary muscle in Visante Anterior Segment Optical Coherence Tomography images. METHODS: Geometric distortions in Visante images analyzed as binary files were assessed by imaging an optical flat and human donor tissue. The appropriate pixel/mm conversion factor to use for air (n = 1) was estimated by imaging calibration spheres. A semiautomatic algorithm was developed to extract the dimensions of the ciliary muscle from Visante images. Measurements were also made manually using Visante software calipers. Interclass correlation coefficients and Bland-Altman analyses were used to compare the methods. A multilevel model was fitted to estimate the variance of algorithm measurements that was due to differences within- and between-examiners in scleral spur selection vs. biological variability. RESULTS: The optical flat and the human donor tissue were imaged and appeared without geometric distortions in binary file format. Bland-Altman analyses revealed that caliper measurements tended to underestimate ciliary muscle thickness at 3 mm posterior to the scleral spur in subjects with the thickest ciliary muscles (t = 3.6, p < 0.001). The percent variance due to within- or between-examiner differences in scleral spur selection was found to be small (6%) when compared with the variance because of biological difference across subjects (80%). Using the mean of measurements from three images, achieved an estimated interclass correlation coefficient of 0.85. CONCLUSIONS: The semiautomatic algorithm successfully segmented the ciliary muscle for further measurement. Using the algorithm to follow the scleral curvature to locate more posterior measurements is critical to avoid underestimating thickness measurements. This semiautomatic algorithm will allow for repeatable, efficient, and masked ciliary muscle measurements in large datasets.


Assuntos
Algoritmos , Corpo Ciliar/anatomia & histologia , Músculo Liso/anatomia & histologia , Tomografia de Coerência Óptica , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Esclera/anatomia & histologia , Software , Pesos e Medidas/instrumentação , Adulto Jovem
17.
Brain Cogn ; 72(1): 36-45, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19942335

RESUMO

Gyrification is the process by which the brain undergoes changes in surface morphology to create sulcal and gyral regions. The period of greatest development of brain gyrification is during the third trimester of pregnancy, a period of time in which the brain undergoes considerable growth. Little is known about changes in gyrification during childhood and adolescence, although considering the changes in gray matter volume and thickness during this time period, it is conceivable that alterations in the brain surface morphology could also occur during this period of development. The formation of gyri and sulci in the brain allows for compact wiring that promotes and enhances efficient neural processing. If cerebral function and form are linked through the organization of neural connectivity, then alterations in neural connectivity, i.e., synaptic pruning, may also alter the gyral and sulcal patterns of the brain. This paper reviews developmental theories of gyrification, computational techniques for measuring gyrification, and the potential interaction between gyrification and neuronal connectivity. We also present recent findings involving alterations in gyrification during childhood and adolescence.


Assuntos
Desenvolvimento do Adolescente , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil , Adolescente , Animais , Criança , Humanos , Modelos Neurológicos , Caracteres Sexuais
18.
J Math Biol ; 60(6): 881-907, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19685243

RESUMO

Cell cycle is controlled at two restriction points, R (1) and R (2). At both points the cell will commit apoptosis if it detects irreparable damage. But at R (1) an undamaged cell also decides whether to proceed to the S phase or go into a quiescent mode, depending on the environmental conditions (e.g., overpopulation, hypoxia). We consider the effect of this decision at the population level in a spherical tissue {r < R(t)}. We prove that if the cells have full control at R (1), they can manipulate the size of R(t) to ensure that 0 < c

Assuntos
Ciclo Celular , Simulação por Computador , Modelos Biológicos , Animais , Apoptose , Humanos
19.
Proc Natl Acad Sci U S A ; 106(29): 12091-6, 2009 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-19597143

RESUMO

Reconstructive microsurgery is a clinical technique used to transfer large amounts of a patient's tissue from one location used to another in order to restore physical deformities caused by trauma, tumors, or congenital abnormalities. The trend in this field is to transfer tissue using increasingly smaller blood vessels, which decreases problems associated with tissue harvest but increases the possibility that blood supply to the transferred tissue may not be adequate for healing. It would thus be helpful to surgeons to understand the relationship between the tissue volume and blood vessel diameter to ensure success in these operations. As a first step towards addressing this question, we present a simple mathematical model that might be used to predict successful tissue transfer based on blood vessel diameter, tissue volume, and oxygen delivery.


Assuntos
Modelos Cardiovasculares , Oxigênio/metabolismo , Procedimentos de Cirurgia Plástica/métodos , Artérias/anatomia & histologia , Artérias/fisiologia , Transporte Biológico , Simulação por Computador , Retalhos Cirúrgicos/irrigação sanguínea
20.
Comput Med Imaging Graph ; 33(7): 520-31, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19482457

RESUMO

In this paper, we propose an improved region-based active contour model in a variational level set formulation. We define an energy functional with a local intensity fitting term, which induces a local force to attract the contour and stops it at object boundaries, and an auxiliary global intensity fitting term, which drives the motion of the contour far away from object boundaries. Therefore, the combination of these two forces allows for flexible initialization of the contours. This energy is then incorporated into a level set formulation with a level set regularization term that is necessary for accurate computation in the corresponding level set method. The proposed model is first presented as a two-phase level set formulation and then extended to a multi-phase formulation. Experimental results show the advantages of our method in terms of accuracy and robustness. In particular, our method has been applied to brain MR image segmentation with desirable results.


Assuntos
Encéfalo/anatomia & histologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/estatística & dados numéricos , Reconhecimento Automatizado de Padrão/métodos
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